V13 Russia rAd26 and rAd5/ COVID-19 Vaccine
Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomized phase 1/2 studies from Russia
Developed a heterologous COVID-19 vaccine consisting of 2 components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector.
Both carry the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S).
Two formulations (in ice and lyophilized) of this vaccine
Two open, non-randomized phase 1/2 studies at two hospitals in Russia. Healthy adult volunteers (men and women) aged 18–60 years to both studies.
Phase 1 of each study, intramuscularly on day 0 either one dose of rAd26-S or one dose of rAd5-S and assessed the safety of the two components for 28 days.
Phase 2 of the study, which began no earlier than 5 days after phase 1 vaccination, administered intramuscularly a prime-boost vaccination, with rAd26-S given on day 0 and rAd5-S on day 21
Results
76 participants to the 2 studies (38 in each study). In each study, nine volunteers received rAd26-S in phase 1, nine received rAd5-S in phase 1, and 20 received rAd26-S and rAd5-S in phase 2. Both vaccine formulations were safe and well tolerated
Antibodies
All participants produced antibodies to SARS-CoV-2 glycoprotein.
At day 42, receptor binding domain-specific IgG titres were 14 703 with the cold formulation and 11 143 with the lyophilized formulation, and neutralizing antibodies were 49·25 with the frozen formulation and 45·95 with the lyophilized formulation, with a seroconversion rate of 100%.
Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4+ and 1·3% CD8+ with the frozen formulation, and a median cell proliferation of 1·3% CD4+ and 1·1% CD8+ with the lyophilized formulation.
Several candidate COVID-19 vaccines have been tested in clinical trials
Ad5 Adenovirus type 5 (Ad5) vector-based vaccine (Can-Sino Biological/Beijing Institute of Biotechnology, China)
Ad26 vector-based vaccine (Johnson & Johnson, USA)
Vaccine containing a simian adenoviral vector (AstraZeneca/University of Oxford, UK)
Candidate COVID-19 vaccines based on different platforms (vectored, DNA, mRNA, inactivated, etc.) were being tested in clinical trials.
Prevention of SARS-CoV-2 infection might be achieved by targeting the spike protein (glycoprotein S), which interacts with the ACE2 receptor and enables entry of SARS-CoV-2 into the cell. Blocking this interaction decreases viral internalization and replication. Most vaccines that are currently in development target glycoprotein S as the main antigen.
Glycoprotein S consists of two subunits: S1 contains a receptor-binding domain (RBD), which interacts with the ACE2 receptor on the cell surface; S2 mediates the fusion of viral and cell membranes via formation of a six-helix bundle fusion core. To protect against SARS-CoV-2 infection, it is important to form neutralizing antibodies targeting S1 RBD, S1 N-terminal domain, or the S2 region; these antibodies block binding of the RBD to the ACE2 receptor and prevent S2-mediated membrane fusion or entry into the host cell, thus inhibiting viral infection.
A full dose of the vaccine was 1011 viral particles per dose for both recombinant adenoviruses and all participants received full doses.
The vaccine was manufactured as two formulations, frozen (Gam-COVID-Vac) and lyophilized (Gam-COVID-Vac-Lyo). The cold vaccine has a volume of 0·5 mL (per dose) and the lyophilized vaccine needs to be reconstituted in 1·0 mL of sterile water for injection (per dose).
Antigen-specific humoral immune responses were analyzed on days 0, 14, 21, and 28 in phase 1 and on days 0, 14, 21, 28, and 42 in phase 2.
The titre of neutralizing antibodies was measured on days 0, 14, and 28 in phase 1 and on days 0, 14, 28, and 42 in phase 2
Cell-mediated immune responses were measured on days 0, 14, and 28 after the first injection by determination of antigen-specific proliferating CD4+ and CD8+ cells by flow cytometry and by quantification of interferon-γ release.
When analyzing antigen-specific IgGs, the seroconversion rate was 100% for both vaccine formulations on days 28 and 42 of the study, and when analyzing neutralizing antibody responses, seroconversion was 100% on day 42 of the study for both vaccine formulations.
Cellular immune responses showed formation of antigen-specific cells of both T-helper (CD4+) and T-killer (CD8+) cells, and an increase in the concentration of interferon-γ secretion in peripheral blood mononuclear cells, in 100% of volunteers.
